Project Summary The vertebrate large intestine is host to a large microbial community that confers benefit by functioning in host nutrition, immune education and colonization resistance against enteric pathogens. The composition of the gut microbiota varies with the diet, but little is known about how shifts in the microbiota composition affect functionality, such as the ability to confer colonization resistance against enteric pathogens. Here we will investigate how dietary copper supplementation, a common practice to improve growth performance in livestock, alters colonization resistance against the enteric pathogen Salmonella enterica serovar (S.) Typhimurium. Our central hypothesis is that dietary copper supplementation depletes propionate- producing Bacteroidaceae from the gut microbiota, thereby conferring a fitness advantage for S. Typhimurium strains carrying the sopE gene. We will test key aspects of our hypothesis and accomplish the objectives of this application using the logical and innovative approach outlined in the following specific aim: Determine whether a dietary copper-induced Bacteroidaceae depletion lowers colonization resistance against S. Typhimurium lysogenized with a sopE-encoding prophage. It is our expectation that the outcome of our experiments will show that diet-induced shifts in the gut microbiota composition in livestock can select for enteric pathogens carrying new virulence factors, which is relevant for human health because livestock carriage is a common route for introducing the pathogen into our food supply. This outcome will be significant because it will usher in the novel concept that diet-induced shifts in the microbiota composition can select for new virulence factors in enteric pathogens, a paradigm of broad interest to researchers in bacterial pathogenesis, microbiota and nutrition.